CC BY-NC-ND 4.0 · Thromb Haemost 2022; 122(04): 646-656
DOI: 10.1055/a-1647-9896
Trial Protocol Design Paper

Extended Anticoagulant Treatment with Full- or Reduced-Dose Apixaban in Patients with Cancer-Associated Venous Thromboembolism: Rationale and Design of the API-CAT Study

1   Service de Médecine Interne, Hôpital Louis Mourier, AP-HP, Colombes, France
2   Université de Paris, Paris, France
3   Innovative Therapies in Haemostasis, INSERM UMR_S1140, Paris, France
4   INNOVTE-FCRIN, Saint-Etienne, France
,
Giancarlo Agnelli
5   Internal Vascular and Emergency Medicine – Stroke Unit, University of Perugia, Perugia, Italy
,
Cihan Ay
6   Clinical Division of Haematology and Haemostaseology, Department of Medicine I, Comprehensive Cancer Center Vienna, Medical University of Vienna, Vienna, Austria
,
7   2nd Propaedeutic Department of Medicine, ATTIKON University Hospital, National & Kapodistrian University of Athens, Athens, Greece
,
Cecilia Becattini
5   Internal Vascular and Emergency Medicine – Stroke Unit, University of Perugia, Perugia, Italy
,
Marc Carrier
8   Department of Medicine, Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario, Canada
,
Céline Chapelle
9   Unité de Recherche Clinique Innovation et Pharmacologie, CHU de Saint-Etienne, Saint-Etienne, France
10   SAINBIOSE INSERM U1059, Université Jean Monnet, Université de Lyon, Saint-Etienne, France
,
Alexander T. Cohen
11   Guy's and St. Thomas' NHS Foundation Trust Hospital, King's College London, London, United Kingdom
,
Philippe Girard
12   Département de Pneumologie, Institut Mutualiste Montsouris, Paris, France
,
Menno V. Huisman
13   Department of Medicine − Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, The Netherlands
,
13   Department of Medicine − Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, The Netherlands
,
Juan J. López-Núñez
14   Department of Internal Medicine, Hospital Universitari Germans Trias i Pujol, Badalona, Spain
15   Department of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain
,
Anthony Maraveyas
16   Queen's Centre for Oncology and Haematology, Hull University Teaching Hospitals NHS Trust, Hull York Medical School, Cottingham, Hull, United Kingdom
,
Didier Mayeur
17   Centre Georges-Francois Leclerc, Dijon, France
,
Olivier Mir
18   Institut Gustave-Roussy, Paris, France
,
Manuel Monreal
14   Department of Internal Medicine, Hospital Universitari Germans Trias i Pujol, Badalona, Spain
15   Department of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain
19   Universidad Católica de Murcia, Murcia, Spain
,
Marc Righini
20   Division of Angiology and Hemostasis, Faculty of Medicine, Geneva University Hospitals, Geneva, Switzerland
,
Charles M. Samama
21   Intensive Care and Perioperative Medicine, Department of Anaesthesia, Hôpital Cochin, GHU AP-HP Centre-Université de Paris, Paris, France
,
Kostas Syrigos
22   Department of Medicine, Sotiria General Hospital, Athens School of Medicine, National & Kapodistrian University, Athens, Greece
,
Sebastian Szmit
23   Departments of Pulmonary Circulation, Thromboembolic Diseases, and Cardiology, Centre of Postgraduate Medical Education, European Health Centre, Otwock, Poland
,
Adam Torbicki
23   Departments of Pulmonary Circulation, Thromboembolic Diseases, and Cardiology, Centre of Postgraduate Medical Education, European Health Centre, Otwock, Poland
,
24   Vascular Medicine and Haemostasis, University Hospitals Leuven, Leuven, Belgium
,
Eric Vicaut
25   URC Lariboisière – Saint-Louis, AP-HP, Université de Paris, Paris, France
,
Tzu-Fei Wang
8   Department of Medicine, Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario, Canada
,
Guy Meyer
2   Université de Paris, Paris, France
4   INNOVTE-FCRIN, Saint-Etienne, France
26   Hôpital Européen Georges Pompidou, APHP, Sorbonne Paris Cité, Paris, France
,
Silvy Laporte
4   INNOVTE-FCRIN, Saint-Etienne, France
9   Unité de Recherche Clinique Innovation et Pharmacologie, CHU de Saint-Etienne, Saint-Etienne, France
10   SAINBIOSE INSERM U1059, Université Jean Monnet, Université de Lyon, Saint-Etienne, France
› Author Affiliations
Funding Funding for the study is provided by the BMS–Pfizer Alliance. Tablets of apixaban are provided by Bristol-Myers Squibb and are packaged under AP-HP's responsibility. Bristol-Myers Squibb and Pfizer did not have any role in the study design, study conduction, data collection, or analysis.

Abstract

Cancer-associated thrombosis (CT) is associated with a high risk of recurrent venous thromboembolic (VTE) events that require extended anticoagulation in patients with active cancer, putting them at risk of bleeding. The aim of the API-CAT study (NCT03692065) is to assess whether a reduced-dose regimen of apixaban (2.5 mg twice daily [bid]) is noninferior to a full-dose regimen of apixaban (5 mg bid) for the prevention of recurrent VTE in patients with active cancer who have completed ≥6 months of anticoagulant therapy for a documented index event of proximal deep-vein thrombosis and/or pulmonary embolism. API-CAT is an international, randomized, parallel-group, double-blind, noninferiority trial with blinded adjudication of outcome events. Consecutive patients are randomized to receive apixaban 2.5 or 5 mg bid for 12 months. The primary efficacy outcome is a composite of recurrent symptomatic or incidental VTE during the treatment period. The principal safety endpoint is clinically relevant bleeding, defined as a composite of major bleeding or nonmajor clinically relevant bleeding. Assuming a 12-month incidence of the primary outcome of 4% with apixaban and an upper limit of the two-sided 95% confidence interval of the hazard ratio <2.0, 1,722 patients will be randomized, assuming an up to 10% loss in total patient-years (β = 80%; α one-sided = 0.025). This trial has the potential to demonstrate that a regimen of extended treatment for patients with CT beyond an initial 6 months, with a reduced apixaban dose, has an acceptable risk of recurrent VTE recurrence and decreases the risk of bleeding.

Supplementary Material



Publication History

Received: 27 May 2021

Accepted: 08 July 2021

Accepted Manuscript online:
17 September 2021

Article published online:
05 November 2021

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